Wiener medizinische Wochenschrift
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Host defense and blood coagulation are tightly connected and interacting systems, necessary for the integrity of an organism. Complex mechanisms regulate the intensity of a host response to invading pathogens or other potentially dangerous situations. Under regular conditions, this response is limited in time and located to the site of injury. ⋯ Septic organ dysfunction is caused by intravascular fibrin deposition as a result of coagulation activation, anticoagulant breakdown, and shut down of fibrinolysis. This article describes the major pathophysiologic reactions in these situations and presents www. SepDIC.eu, an online tool on sepsis and associated coagulopathy.
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Mitochondria are the key source of cellular ATP and their structure and function are markedly affected by pathophysiologic processes associated with the host's response to invading pathogens. In particular, the highly reactive compound peroxynitrite, generated by the reaction of nitric oxide and superoxide anions, inhibits mitochondrial enzymes and damages lipids, proteins, and nucleic acids. ⋯ This process consumes large amounts of nicotinamide adenine dinucleotide (NAD(+)) leading to cellular NAD(+) depletion that impairs flux of reducing equivalents into the respiratory chain and also further promotes inflammation. In experimental studies, novel therapeutic strategies that aim to ameliorate the host's pathogen response or to modulate intracellular signaling events related to oxidative stress protected mitochondrial function and preserved cellular respiration ultimately leading to improved organ function.
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Wien Med Wochenschr · Mar 2010
ReviewUpdate on the role of Toll-like receptors during bacterial infections and sepsis.
Toll-like receptors (TLRs) are recognition molecules that importantly contribute to the innate immune response to bacterial and viral infections. Once TLRs sense the presence of invading pathogens a signal transduction cascade is initiated that eventually leads to the production of pro-inflammatory mediators and attraction of neutrophils to the site of infection. While the ultimate goal of this defense pathway is the successful elimination of invading microbes, prolonged or exaggerated stimulation of TLR-associated events can lead to systemic inflammation and clinical symptoms of sepsis. This brief review summarizes the impact of selected TLRs in the host response to clinically important bacteria and provides insights into TLR-associated therapeutic approaches during sepsis and inflammation.